Department of Biochemistry and Molecular Biology, University of Texas-McGovern Medical School, 6431 Fannin Street, Suite 6.200, Houston, TX, 77030, USA.
Cooper Medical School of Rowan University, 401 Broadway, Camden, NJ, 08103, USA.
Mol Biol Rep. 2020 Aug;47(8):6471-6478. doi: 10.1007/s11033-020-05691-1. Epub 2020 Aug 12.
S-acylation reversible-post-translational lipidation of cysteine residues-is emerging as an important regulatory mechanism in T cell signaling. Dynamic S-acylation is critical for protein recruitment into the T cell receptor complex and initiation of the subsequent signaling cascade. However, the enzymatic control of protein S-acylation in T cells remains poorly understood. Here, we report a previously uncharacterized role of DHHC21, a member of the mammalian family of DHHC protein acyltransferases, in regulation of the T cell receptor pathway. We found that loss of DHHC21 prevented S-acylation of key T cell signaling proteins, resulting in disruption of the early signaling events and suppressed expression of T cell activation markers. Furthermore, downregulation of DHHC21 prevented activation and differentiation of naïve T cells into effector subtypes. Together, our study provides the first direct evidence that DHHC protein acyltransferases can play an essential role in regulation of T cell-mediated immunity.
半胱氨酸残基的 S-酰化可逆翻译后脂质化——作为 T 细胞信号转导的重要调节机制正在出现。动态 S-酰化对于蛋白质募集到 T 细胞受体复合物并启动随后的信号级联反应至关重要。然而，T 细胞中蛋白质 S-酰化的酶控制仍知之甚少。在这里，我们报告了 DHHC21 的一个以前未被描述的作用，DHHC21 是哺乳动物 DHHC 蛋白酰基转移酶家族的成员，在调节 T 细胞受体途径中的作用。我们发现，DHHC21 的缺失阻止了关键 T 细胞信号蛋白的 S-酰化，导致早期信号事件中断，并抑制了 T 细胞激活标志物的表达。此外，DHHC21 的下调阻止了初始 T 细胞向效应子亚型的激活和分化。总之，我们的研究首次直接证明 DHHC 蛋白酰基转移酶在调节 T 细胞介导的免疫中可以发挥重要作用。
